The present invention is in the field of enzyme proteins that are related to the trans-prenyltransferase subfamily, recombinant DNA molecules, and protein production. The present invention specifically provides novel peptides and proteins and nucleic acid molecules encoding such peptide and protein molecules, all of which are useful in the development of human therapeutics and diagnostic compositions and methods.
Many human enzymes serve as targets for the action of pharmaceutically active compounds. Several classes of human enzymes that serve as such targets include helicase, steroid esterase and sulfatase, convertase, synthase, dehydrogenase, monoxygenase, transferase, kinase, glutanase, decarboxylase, isomerase and reductase. It is therefore important in developing new pharmaceutical compounds to identify target enzyme proteins that can be put into high-throughput screening formats. The present invention advances the state of the art by providing novel human drug target enzymes related to the trans-prenyltransferase subfamily.
The present invention has substantial similarity to trans-prenyltransferase (polyprenyl pyrophosphate synthetase). Trans-prenyltransferase synthesizes the side-chain moiety of coenzyme Q, taking place in microsomes of Golgi system. Trans-prenyltransferase, a ubiquitous protein, is a member of the coenzyme Q biosynthesis pathway, and a very important enzyme involved in biosynthesis of polyprenyls and coenzyme Q. CoQ synthesis is also dependent on trans-prenyltransferase activity on the level of intracellular substrate concentration. In addition, CoQ level may be regulated in blood as well as in various tissues. Thus, the enzyme of the present invention may be a potential drug target for anti-cancer treatment. For a review related to trans-prenyltransferase, see Appelkvist et al., Mol Aspects Med 1994;15 Suppl:s37-46; Rotig et al., Lancet Jul. 29, 2000;356(9227):391-5.
Enzyme proteins, particularly members of the trans-prenyltransferase subfamily, are a major target for drug action and development. Accordingly, it is valuable to the field of pharmaceutical development to identify and characterize previously unknown members of this subfamily of enzyme proteins. The present invention advances the state of the art by providing previously unidentified human enzyme proteins, and the polynucleotides encoding them, that have homology to members of the trans-prenyltransferase subfamily. These novel compositions are useful in the diagnosis, prevention and treatment of biological processes associated with human diseases.
The present invention is based in part on the identification of amino acid sequences of human enzyme peptides and proteins that are related to the trans-prenyltransferase subfamily, as well as allelic variants and other mammalian orthologs thereof. These unique peptide sequences, and nucleic acid sequences that encode these peptides, can be used as models for the development of human therapeutic targets, aid in the identification of therapeutic proteins, and serve as targets for the development of human therapeutic agents that modulate enzyme activity in cells and tissues that express the enzyme. Experimental data as provided in FIG. 1 indicates expression in humans in the T cells from T cell leukemia, B cells from Burkitt lymphoma, neuroblastoma cells, duodenal adenocarcinioma cell line, adenocarcinoma cell line, stomach, breast, whole liver.